Tuning in C-nociceptors to reveal mechanisms in chronic neuropathic pain

Journal article

Publication Details

Author(s): Jonas R, Namer B, Stockinger L, Chisholm K, Schnakenberg M, Landmann G, Kucharczyk M, Konrad C, Schmidt R, Carr R, Mcmahon S, Schmelz M, Rukwied R
Journal: Annals of Neurology
Publication year: 2018
Volume: 83
Journal issue: 5
Pages range: 945-957
ISSN: 0364-5134


OBJECTIVE: Develop and validate a low-intensity sinusoidal electrical stimulation paradigm to preferentially activate C-fibers in human skin.
METHODS: Sinusoidal transcutaneous stimulation (4Hz) was assessed psychophysically in healthy volunteers (n = 14) and neuropathic pain patients (n = 9). Pursuing laser Doppler imaging and single nociceptor recordings in vivo in humans (microneurography) and pigs confirmed the activation of "silent" C-nociceptors. Synchronized C-fiber compound action potentials were evoked in isolated human nerve fascicles in vitro. Live cell imaging of L4 dorsal root ganglia in anesthetized mice verified the recruitment of small-diameter neurons during transcutaneous 4-Hz stimulation of the hindpaw (0.4mA).
RESULTS: Transcutaneous sinusoidal current (0.05-0.4mA, 4Hz) activated "polymodal" C-fibers (50% at ∼0.03mA) and "silent" nociceptors (50% at ∼0.04mA), intensities substantially lower than that required with transcutaneous 1-ms rectangular pulses ("polymodal" ∼3mA, "silent" ∼50mA). The stimulation induced delayed burning (nonpulsating) pain and a pronounced axon-reflex erythema, both indicative of C-nociceptor activation. Pain ratings to repetitive stimulation (1 minute, 4Hz) adapted in healthy volunteers by Numeric Rating Scale (NRS) -3 and nonpainful skin sites of neuropathic pain patients by NRS -0.5, whereas pain even increased in painful neuropathic skin by approximately NRS +2.
INTERPRETATION: Sinusoidal electrical stimulation at 4Hz enables preferential activation of C-nociceptors in pig and human skin that accommodates during ongoing (1-minute) stimulation. Absence of such accommodation in neuropathic pain patients suggest axonal hyperexcitability that could be predictive of alterations in peripheral nociceptor encoding and offer a potential therapeutic entry point for topical analgesic treatment. Ann Neurol 2018;83:945-957.

FAU Authors / FAU Editors

Namer, Barbara PD Dr.
Lehrstuhl für Physiologie

External institutions with authors

King’s College London
Luzerner Kantonsspital
Ruprecht-Karls-Universität Heidelberg
Schweizer Paraplegiker-Zentrum
Uppsala University

How to cite

Jonas, R., Namer, B., Stockinger, L., Chisholm, K., Schnakenberg, M., Landmann, G.,... Rukwied, R. (2018). Tuning in C-nociceptors to reveal mechanisms in chronic neuropathic pain. Annals of Neurology, 83(5), 945-957. https://dx.doi.org/10.1002/ana.25231

Jonas, Robin, et al. "Tuning in C-nociceptors to reveal mechanisms in chronic neuropathic pain." Annals of Neurology 83.5 (2018): 945-957.


Last updated on 2019-26-02 at 08:08